study in patients with depression not responding to selective serotonin re-uptake inhibitors

Conditions: Depressive Disorder

Summary: this study is designed to evaluate the efficacy and safety in depressive patients who did not respond sufficiently to selective serotonin re-uptake inhibitors (ssri).


Eligibility criteria:
inclusion criteria: * \[at the start of the pretreatment phase\] * target disease: patients diagnosed as having the following primary disease on the basis of dsm-iv-tr criteria. * major depressive disorder, single episode (296.2x) (excluding with psychotic features) * major depressive disorder, recurrent (296.3x) (excluding with psychotic features) * ham-d (17 items) total score is \>=16. * patients who have been treated with marketed paroxetine (paxil®) at 20mg/day to 40mg/day for 4 weeks and more at the start of the pretreatment phase. * age: \>=18 years old (at the time of informed consent) , \<65 years old (at the start of treatment phase ) * gender: male or female. * inpatients or outpatients: either * informed consent: the subject himself/herself must give written informed consent. however, if the subject is under 20 at the time of giving consent, both the subject himself/herself and his/her legally acceptable representative must give written informed consent. \[at the end of the pretreatment phase\] 1. ham-d (17 items) total score is ≥14. 2. percentage of change from the start of the pretreatment phase in the ham-d (17 items) total score is \<50% \[at the start of the treatment phase\] 1. ham-d (17 items) total score is ≥14. 2. percentage of change from the start of the pretreatment phase in the ham-d (17 items) total score is \<50% exclusion criteria: \[at the start of the pre-treatment phase\] * patients with a complication of glaucoma * patients concomitantly using a drug increasing the risk of bleeding and patients with bleeding tendency or predisposition to bleeding * patients with predisposition to seizure (who currently have or have a past history of seizure, febrile convulsive seizure in infancy, cerebral tumour, cerebrovascular disorder or head injury, who have a family history of idiopathic seizure, patients with diabetes who have been treated with oral hypoglycaemics or insulin, or who use drugs lowering the threshold of seizure). * patients who currently have or have a past history of the following disorders: * anorexia nervosa (dsm-iv-tr 307.1) * bulimia nervosa (dsm-iv-tr 307.51) * patients with a history of manic episode * patients with a past or current dsm- iv-tr diagnosis of schizophrenia or other psychotic disorder * patients with a current dsm-iv-tr axis ii diagnosis (e.g., antisocial or borderline personality disorder) * patients starting psychotherapy (except for supportive psychotherapy not aimed at therapeutic efficacy and unlikely to affect efficacy evaluation) and formal cognitive behaviour therapy within 5 weeks prior to the start of the pre-treatment phase * patients with a diagnosis of substance abuse (alcohol or drug) by the dsm-iv-tr criteria or with a diagnosis of substance dependence within 1 year prior to the start of the pre-treatment phase * patients who have received electroconvulsive therapy within 17 weeks prior to the start of the pre-treatment phase * patients who have taken mao inhibitors (selegiline hydrochloride) within 2 weeks prior to the start of the pre-treatment phase * patients who have taken another investigational drug within 12 weeks prior to the start of the pre-treatment phase * female patients who are pregnant, possibly pregnant or are nursing, and those who want to become pregnant before 30 days after the last dose of the investigational product * patients who have attempted suicide within 17 weeks prior to the start of the pre-treatment phase, or patients for whom the score of suicide-related item no. 3 of ham-d is \>=3, or patients in whom the risk of suicide is judged to be high by the investigator (sub-investigator) * patients in whom the risk of homicide is judged to be high by the investigator (sub-investigator) * patients with a history of hypersensitivity to 323u66 and/or paroxetine * patients with serious cerebral disease * patients who have ecg or clinical evidence of any cardiac condition that the investigator (sub-investigator) feels may predispose the subject to ischemia or arrhythmia * patients with serious physical symptoms (i.e. cardiac/hepatic/renal disorder, hematopoietic disorder) the index of seriousness is grade 3 of "criteria for classification of seriousness of adverse drug reactions to pharmaceutical products, etc." (pab/psd no.80 in 1992). * patients with a history or complication of cancer or malignant tumour. * patients whose major depressive disorder is due to direct physiological effects of a general medical condition (for example, hypothyroidism, parkinson's disease, chronic pain) * patients with systolic blood pressure of \>=160 mmhg or diastolic blood pressure of \>=100 mmhg * patients who are inappropriate for participating in the study in the judgement of the investigator (sub-investigator) \[at the start of the treatment phase\] 1. patients whose compliance of paroxetine during the pretreatment phase is less than 70%. 2. patients who have ecg or clinical evidence of any cardiac condition that the investigator (sub-investigator) feels may predispose the subject to ischemia or arrhythmia 3. patients with systolic blood pressure of \>=160 mmhg or diastolic blood pressure of \>=100 mmhg

Keywords: depression double-blind placebo-controlled bupropion hydrochloride ssri comparative study non-responder